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To address the limitations of whole-spike COVID vaccines, here comes a new mRNA vaccines encoding membrane-anchored receptor-binding domain (RBD-TMs), each a fusion of a variant RBD, the transmembrane (TM) and cytoplasmic tail (CT) fragments of the SARS-CoV-2 spike protein. 1/ 
In mice, RBD-TM mRNA vaccines against ancestral, Beta, Delta, Delta-plus, Kappa, Omicron BA.1 or BA.5, all induced strong humoral responses against the target RBD.
Viral neutralization assays indicated broad neutralizing activity against a range of variant RBDs 2/
Viral neutralization assays indicated broad neutralizing activity against a range of variant RBDs 2/
Notably, the RBD-TM vaccines were able to overcome the detrimental effects of immune imprinting. 3/
Each RBD-TM mRNA is 28% of the length of its whole-spike equivalent. This advantage will enable tetravalent mRNA vaccines to be developed at well-tolerated doses of mRNA.
➡️ This will also allow multivalent vaccines to be produced without risking increased reactogenicity. 4/
➡️ This will also allow multivalent vaccines to be produced without risking increased reactogenicity. 4/
The challenge will be to outflank the RBD mutation of the virus by anticipating the emergence of evasive mutants, making use of the developing knowledge of likely hot-spots in the RBD, & deep scans that identify which mutations are tolerated without loss of ACE2 binding. 5/
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